Cryptosporidium: Still Open Scenarios

Pane, Stefania; Putignani, Lorenza

doi:10.3390/pathogens11050515

Cited by 21 publications

(16 citation statements)

References 118 publications

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“…Cryptosporidiosis, an enteric disease caused by a protozoan gut trophic parasite, is often seen as other enteric pathogens with or without overt symptoms in undernourished children in their first years of life, causing chronic enteric inflammation with or without diarrhea, especially when children are being weaned from exclusive breastfeeding to contaminated water and food [40,41]. Growth declines, even without diarrhea, are frequently associated with cryptosporidiosis in children in adverse environments.…”

Section: Vicious Cycle Of Malnutrition and Enteric Diseases 21 Prolon...mentioning

confidence: 99%

ApoE Mimetic Peptides to Improve the Vicious Cycle of Malnutrition and Enteric Infections by Targeting the Intestinal and Blood-Brain Barriers

et al. 2023

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Apolipoprotein E (apoE) mimetic peptides are engineered fragments of the native apoE protein’s LDL-receptor binding site that improve the outcomes following a brain injury and intestinal inflammation in a variety of models. The vicious cycle of enteric infections and malnutrition is closely related to environmental-driven enteric dysfunction early in life, and such chronic inflammatory conditions may blunt the developmental trajectories of children with worrisome and often irreversible physical and cognitive faltering. This window of time for microbiota maturation and brain plasticity is key to protecting cognitive domains, brain health, and achieving optimal/full developmental potential. This review summarizes the potential role of promising apoE mimetic peptides to improve the function of the gut-brain axis, including targeting the blood-brain barrier in children afflicted with malnutrition and enteric infections.

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Section: Vicious Cycle Of Malnutrition and Enteric Diseases 21 Prolon...mentioning

confidence: 99%

ApoE Mimetic Peptides to Improve the Vicious Cycle of Malnutrition and Enteric Infections by Targeting the Intestinal and Blood-Brain Barriers

et al. 2023

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“…The phylum Apicomplexa represents a group of divergent parasitic protists comprising multiple species of medical and agricultural importance: Plasmodium parasites cause malaria and are responsible for over half a million deaths each year in mostly lowincome countries (World Health Organization, 2021); Cryptosporidium parasites cause cryptosporidiosis-a leading cause of childhood diarrhoea and malnutrition worldwide (Pane & Putignani, 2022); and Toxoplasma gondii, which causes toxoplasmosis and establishes a latent infection, which can be life-threatening in immunocompromised patients (Montoya & Liesenfeld, 2004). These eukaryotic intracellular parasites encode their own ubiquitination machinery; however, the role of ubiquitination in parasite homeostasis and pathogenesis is still unclear.…”

Section: Introductionmentioning

confidence: 99%

Characterisation of the OTU domain deubiquitinase complement ofToxoplasma gondii

et al. 2023

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The phylum Apicomplexa contains several parasitic species of medical and agricultural importance. The ubiquitination machinery remains, for the most part, uncharacterised in apicomplexan parasites, despite the important roles that it plays in eukaryotic biology. Bioinformatic analysis of the ubiquitination machinery in apicomplexan parasites revealed an expanded ovarian tumour domain–containing (OTU) deubiquitinase (DUB) family inToxoplasma, potentially reflecting functional importance in apicomplexan parasites. This study presents comprehensive characterisation ofToxoplasmaOTU DUBs. AlphaFold-guided structural analysis not only confirmed functional orthologues found across eukaryotes, but also identified apicomplexan-specific enzymes, subsequently enabling discovery of a cryptic OTU DUB inPlasmodiumspecies. Comprehensive biochemical characterisation of 11ToxoplasmaOTU DUBs revealed activity against ubiquitin- and NEDD8-based substrates and revealed ubiquitin linkage preferences for Lys6-, Lys11-, Lys48-, and Lys63-linked chain types. We show that accessory domains inToxoplasmaOTU DUBs impose linkage preferences, and in case of apicomplexan-specific TgOTU9, we discover a cryptic ubiquitin-binding domain that is essential for TgOTU9 activity. Using the auxin-inducible degron (AID) to generate knockdown parasite lines, TgOTUD6B was found to be important forToxoplasmagrowth.

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“…It spreads by fecal-oral route through contaminated food or water with environmentally resistant oocysts (Efstratiou et al 2017), and rarely by inhalation (Bauerfeind et al 2016). Cryptosporidium is one of the most frequent causes of waterborne diseases (Pane and Putignani 2022). It comes second after rotavirus as a main worldwide cause of moderate-to-severe pediatric diarrhea (Kotloff et al 2019).…”

Section: Introductionmentioning

confidence: 99%

Therapeutic efficacy of proton pump inhibitor (Omeprazole) on cryptosporidiosis parvum in immunosuppressed experimental mice

Beshay

Nassef

Shafey

et al. 2023

Preprint

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Cryptosporidiosis is one of the most frequent food and water-borne diseases. The disease might be life-threatening in immunosuppressed patients. Unfortunately, the only approved drug, nitazoxanide, is with variable efficacies, particularly in malnourished children and immunocompromised patients. Therefore, there is a need to discover an alternative treatment that could be achieved by targeting the metabolic pathways. One of the important enzymes in the glycolysis pathway of C. parvum is triosephosphate isomerase, which could be hindered by the proton pump inhibitor (PPI) omeprazole. In this study, omeprazole was repurposed against C. parvum infection in experimentally immunosuppressed mice. This study was conducted on five mice groups (n = 10). Group I (Normal Control), group II (Infected Control): Mice were infected orally with 1×105 C. parvum oocysts on the 15th day of DEX induced immunosuppression. Group III (NTZ-treated): infected and treated by NTZ. Group IV (Omeprazole-treated), and lastly, Group V (NTZ + Omeprazole-treated). The result obtained with omeprazole alone was better than nitazoxanide regarding oocyst shedding reduction percentages (84.9% & 56.1%, respectively). Also, it was better regarding restoration of histopathological and ultrastructural architectures, improvement of liver enzymes (alanine aminotransferase and aspartate aminotransferase) and renal functions (urea and creatinine), and the reduction of C. parvum triosephosphate isomerase (TIM) gene expression by RT-PCR. However, the best results were obtained with the combined treatment. Hence, omeprazole could be considered a novel drug option to treat this life-threatening parasitic infection either alone or combined with NTZ, especially in immunosuppressed patients.

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Cryptosporidium: Still Open Scenarios

Cited by 21 publications

References 118 publications

ApoE Mimetic Peptides to Improve the Vicious Cycle of Malnutrition and Enteric Infections by Targeting the Intestinal and Blood-Brain Barriers

ApoE Mimetic Peptides to Improve the Vicious Cycle of Malnutrition and Enteric Infections by Targeting the Intestinal and Blood-Brain Barriers

Characterisation of the OTU domain deubiquitinase complement ofToxoplasma gondii

Therapeutic efficacy of proton pump inhibitor (Omeprazole) on cryptosporidiosis parvum in immunosuppressed experimental mice

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